ORGANIC LETTERS
Intramolecular Nitrile Oxide−Alkene Cycloaddition of Sugar Derivatives with Unmasked Hydroxyl Group(s)
2007 Vol. 9, No. 5 753-756
Tony K. M. Shing,* Wai F. Wong, Hau M. Cheng, Wun S. Kwok, and King H. So Department of Chemistry and Center of NoVel Functional Molecules, The Chinese UniVersity of Hong Kong, Shatin, NT, Hong Kong, China
[email protected] Received November 27, 2006
ABSTRACT
Intramolecular nitrile oxide−alkene cycloaddition (INOC) of sugar derivatives with one to four free hydroxyl group(s) is reported. The INOC reaction, using chloramine-T, in the presence of silica gel, to generate nitrile oxides from oximes, proceeded smoothly to afford five- or six-membered carbocycles in good to excellent yields. This new methodology alleviates protection/deprotection steps and makes the synthetic route shorter and more efficient.
Intramolecular nitrile oxide-alkene cycloaddition (INOC) and intramolecular nitrone-alkene cycloaddition (INAC) are versatile synthetic tools for the fabrication of fully functionalized carbocycles of different ring sizes from sugars.1a-c The heavily oxygenated carbocycles prepared via the INOC reaction are valuable precursors for the syntheses of cyclopentanoid and cyclohexanoid natural products and analogues. Examples are cyclophellitol,1d trehazolin,1e (+)-gabosines C and E,1f glycosidase inhibitors aminocyclopentitols,1g and carbocyclic nucleosides noraristeromycin and neplanocin A.1h (1) (a) Gallos, J. K.; Koumbis, A. E. Curr. Org. Chem. 2003, 7, 397426. (b) Ferrier, R. J.; Furneaux, R. H.; Prasit, P.; Tyler, P. C.; Brown, K. L.; Gainsford, G. J.; Diehl, J. W. J. Chem. Soc., Perkin Trans. 1 1983, 1621-1628. (c) Ferrier, R. J.; Prasit, P.; Gainsford, G. J.; Page, Y. L. J. Chem. Soc., Perkin Trans. 1 1983, 1629-1634. (d) Tatsuta, K. Pure Appl. Chem. 1996, 68, 1341-1346. (e) Kobayashi, Y.; Miyazaki, H.; Shiozaki, M. J. Org. Chem. 1994, 59, 813-822. (f) Lygo, B.; Swiatyj, M.; Trabsa, H.; Voyle, M. Tetrahedron Lett. 1994, 35, 4197-4200. (g) Kleban, M.; Hilgers, P.; Greul, J. N.; Kugler, R. D.; Li, J.; Picasso, S.; Vogel, P.; Ja¨ger, V. ChemBioChem 2001, 365-368. (h) Gallos, J. K.; Koumbis, A. E.; Xiraphaki, V. P.; Dellios, C. C.; Coutouli-Argyropoulou, E. Tetrahedron 1999, 55, 15167-15180. (i) Bode, J. W.; Fraefel, N.; Muri, D.; Carreira, E. M. Angew. Chem., Int. Ed. 2001, 40, 2082-2085. (j) Kamimura, A.; Kaneko, Y.; Ohta, A.; Matsuura, K.; Fujimoto, Y.; Kakehi, A.; Kanemasa, S. Tetrahedron 2002, 58, 9613-9620. (k) Kamimura, A.; Kaneko, Y.; Ohta, A.; Kakehi, A.; Matsuda, H.; Kanemasa, S. Tetrahedron Lett. 1999, 40, 4349-4352. 10.1021/ol062873p CCC: $37.00 Published on Web 01/31/2007
© 2007 American Chemical Society
Scheme 1.
Formation of Oximolactone 2 (an Undesired Reaction)
Magnesium ion mediated intermolecular cycloaddition of nitrile oxides with allyl alcohols is known,1i-k but the alcohol in nitrile oxide is protected.1i Most INOC reactions of sugar derivatives proceed with masked hydroxyl groups.1d,g,h,2 Only two examples have been realized in the presence of a free hydroxyl group at the δ position.3 INOC of sugar derivatives with free hydroxyl group(s) present in other positions (2) (a) Peet, N. P.; Huber, E. W.; Farr, R. A. Tetrahedron 1991, 47, 7537-7550. (b) Shing, T. K. M.; Wong, C.-H.; Yip, T. Tetrahedron: Asymmetry 1996, 7, 1323-1340. (c) Shing, T. K. M.; Fung, W. C.; Wong, C. H. J. Chem. Soc., Chem. Commun. 1994, 449-450. (d) Takahashi, T.; Nakazawa, M.; Sakamoto, Y.; Houk, K. N. Tetrahedron Lett. 1993, 34, 4075-4078. (e) Nakata, M.; Akazawa, S.; Kitamura, S.; Tatsuta, K. Tetrahedron Lett. 1991, 32, 5363-5366.
Table 1. INOC of Substrates 3, 5, 7, and 9 under Different Conditions
has not been reported. This paper describes, using chloramine-T/silica gel to generate nitrile oxide from oxime, successful INOC of sugar derivatives with free hydroxyl groups that alleviate protection/deprotection steps which, in turn, renders the various synthetic schemes shorter and more efficient. The nitrile oxides derived from sugars are highly oxygenated, and the free hydroxyl group, when present, could attack
the electrophilic carbon of nitrile oxide 1, forming oximolactone 24 as the side product (Scheme 1 and entry 3 in Table 1). Common reagents for the conversion of oxime into nitrile oxide include NaOCl, NaOCl with NEt3, and N-chlorosuccinimide with NEt3.5 Such reaction conditions are basic enough to deprotonate the hydroxyl function and increase
Table 2. INOC Using Chloramine-T and Silica Gel
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its nucleophilicity. Hence, the formation of the undesired oximolactone product is enhanced. A new nonbasic method for the transformation of oximes derived from sugars into nitrile oxides is therefore warranted. Reaction of oxime 3 with aqueous NaOCl gave an oximolactone that was hydrolyzed immediately to afford lactone 46 in 38% yield (entry 1). Stirring oximes 5 or 9 with aqueous NaOCl resulted in decomposition of the starting material and provided no cycloadducts. Condensation of lactol 7 with NH2OH afforded an oxime that was oxidized with aqueous NaOCl to give the unwanted oximolactone 24 exclusively (entry 3). Chloramine-T7 has been reported for the generation of nitrile oxides from oximes, and by applying such conditions to oxime 5, the oxime derived from lactol 7, and oxime 9, the corresponding isoxazolines 6, 8,8 and 109 were obtained, respectively, but in moderate yields (entries 2, 4, and 5). The formation of the undesired oximolactone 2 might be the major reason for the moderate yields (entry 4). Silica gel was therefore added together with chloramine-T to attain a slightly acidic environment for the INOC reactions of substrates having one to four free hydroxyl group(s), and the results are summarized in Table 2. With this new methodology, isoxazolines 11 and 12 were obtained for the first time from oxime 3 in a combined yield of 79% (entry 6). Oxime 5 now gave a much improved 94% yield of isoxazoline 6 (entry 7, cf. entry 2). Similar improvements in reaction yields were also observed with substrates 7 and 9 (entries 8 and 9). Applying the silica gel mediated reaction conditions to other substrates afforded the desired fivemembered or six-membered carbocycles in good to excellent yields (entries 10-17). For substrate 27, two isoxazolines were obtained after the INOC reaction which were inseparable by column chromatography; these were converted into the acetates 28 and 29 to allow chromatographic separation. The combined overall yield for the four-step transformation was a respectable 73%. All the substrates employed for the INOC reactions were synthesized from carbohydrates, and their preparations are shown in Scheme 2. Diacetonide 32,10 readily available from D-mannose, reacted with excess allylmagnesium bromide to give alkene (3) (a) Duclos, O.; Mondange, M.; Dure´ault, A.; Depezay, J. C. Tetrahedron Lett. 1992, 33, 8061-8064. (b) Tatsuta, K.; Niwata, Y.; Umezawa, K.; Toshima, K.; Nakata, M. Carbohydr. Res. 1991, 222, 189203. (4) The enantiomer of oximolactone 2 was prepared from the oxime with NCS and NEt3 by Professor V. Ja¨ger. See: Gu¨ltekin, Z.; Frey, W.; Ja¨ger, V. Z. Kristallogr. - New Cryst. Struct. 2002, 217, 403-404. (5) Caramella, P.; Gru¨nanger, P. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984; Vol. 1, pp 291-392. (6) Krishna, U. M.; Deodhar, K. D.; Trivedi, G. K. Tetrahedron 2004, 60, 4829-4836. (7) (a) Pal, A.; Bhattacharjee, A.; Bhattacharjya, A.; Patra, A. Tetrahedron 1999, 55, 4123-4132. (b) Majumdar, S.; Mukhopadhyay, R.; Bhattacharjya, A. Tetrahedron 2000, 56, 8945-8951. (8) The X-ray structure of the enantiomer of the acetate derivative of 8 was published by Professor V. Ja¨ger. See: Gu¨ltekin, Z.; Frey, W.; Ja¨ger, V. Z. Kristallogr. - New Cryst. Struct. 2002, 217, 405-406. (9) Structure confirmed by comparing the spectroscopic data of the acetate derivative. See: (a) Henkel, S.; Kleban, M.; Ja¨ger, V. Z. Kristallogr. - New Cryst. Struct. 1997, 212, 53-54. (b) Hilgers, P. Dissertation, Universita¨t Stuttgart, 1996. (c) Kleban, M. Dissertation, Universita¨t Stuttgart, 1996. (10) Schmidt, O. T. Methods in Carbohydrate Chemistry. In Reactions of Carbohydrates; Whistler, R. L., Wolfrom, M. L., Eds.; Academic Press Inc.: New York and London, 1963; Vol. 2, pp 318-319.
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Scheme 2.
Preparation of Substrates
33 with 5:1 diastereoselectivity. Selective hydrolysis of the terminal isopropylidene group in 33, followed by glycol oxidative cleavage, was performed with periodic acid11 in one pot to furnish lactol 34 in 79% yield. Oximation of lactol 34 then gave substrate 3 in quantitative yield. Benzyl-β-Larabinopyranoside 35,12 prepared from glycosidation of L-arabinose, was protected with a trans-diacetal ring to give acetal 36. Upon hydrogenolysis and allylation, alkenes 37 and 23 were harvested from 36 in equal amounts. Alkene 37 was then converted into substrate 5 by glycol oxidative cleavage and oximation. Alkenes 39 and 40, prepared from (11) Wu, W. L.; Wu, Y. L. J. Org. Chem. 1993, 58, 3586-3588. (12) Kawasaki, M.; Matsuda, F.; Terashima, S. Tetrahedron 1988, 44, 5695-5711. 755
according to the literature,13 were readily transformed into substrates 7 and 13 with periodic acid. Iodide 41, constructed from methyl-R-D-glucopyranoside,14 was reacted with zinc15 to give lactol 42 that was converted into substrate 9 after oximation. Substrates 15,13 17,16 and 2016 were prepared from D-ribose according to the literature. Diol 43 was obtained from D-mannose in three steps.17 Glycol oxidative cleavage of diol 43, followed by vinylation, afforded substrates 25 and 27 in equal amounts. Starting from D-galactose, alkene 44 was prepared in three steps.18 Acid hydrolysis of alkene 44 with TFA furnished substrate 30 in 92% yield. To conclude, INOC reactions that use chloramine-T and silica gel in ethanol to generate the nitrile oxide from the D-mannose
(13) Shing, T. K. M.; Elsley, D. A.; Gillhouley, J. G. J. Chem. Soc., Chem. Commun. 1989, 1280-1282. (14) Anisuzzaman, A. K. M.; Whistler, R. L. Carbohydr. Res. 1978, 61, 511-518. (15) (a) Skaanderup, P. R.; Hyldtoft, L.; Madsen, R. Monatsh. Chem. 2002, 133, 467-472. (b) Hyldtoft, L.; Madsen, R. J. Am. Chem. Soc. 2000, 122, 8444-8452. (16) Shing, T. K. M.; Wong, A. W. F.; Ikeno, T.; Yamada, T. J. Org. Chem. 2006, 71, 3253-3263. (17) Suhara, Y.; Kittaka, A.; Ono, K.; Kurihara, M.; Fujishima, T.; Yoshida, A.; Takayama, H. Bioorg. Med. Chem. Lett. 2002, 12, 35333536.
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oxime proceed smoothly with unmasked hydroxyl group(s) to give the desired isoxazolines in good to excellent yields. A general method for the construction of highly functionalized five- and six-membered carbocycles from sugar derivatives via the INOC strategy is now revealed. This new methodology alleviates protection/deprotection steps and makes the entire synthetic avenue shorter and more efficient. Acknowledgment. This work was supported by a grant administered by the Center of Novel Functional Molecules, CUHK. Special thanks go to Prof. V. Ja¨ger of the University of Stuttgart for kindly providing us with the 1H and 13C spectra of the enantiomer of 2, the enantiomer of the acetate derivative of 8, and the acetate derivative of 10 for comparison. Supporting Information Available: Experimental procedures and product characterization. This material is available free of charge via the Internet at http://pubs.acs.org. OL062873P (18) Lee, H. H.; Hodgson, P. G.; Bernacki, R. J.; Korytnyk, W.; Sharma, M. Carbohydr. Res. 1988, 176, 59-72.
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